title: Innate immunity gene polymorphisms and the risk of colorectal neoplasia.
abstract: Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case-control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (OR(per T allele) = 0.68, 95% CI: 0.57-0.83, P = 7.7 × 10(-5), adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (OR(per T allele) = 0.41, 95% CI: 0.30-0.55, P = 2.4 × 10(-) (9)) than for adenoma (OR(per T allele) = 0.84, 95%CI: 0.69-1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (OR(per T allele) = 0.5, 95% CI: 0.37-0.69 and OR(per T allele) = 0.72, 95% CI: 0.54-0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Chang
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Chia
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Krista A
authors.initials: KA
authors.lastname: Zanetti
authors.forename: Bríd M
authors.initials: BM
authors.lastname: Ryan
authors.forename: Julie E
authors.initials: JE
authors.lastname: Goodman
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
authors.forename: Joel
authors.initials: J
authors.lastname: Weissfeld
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Huang
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
mesh_terms: D000236:Adenoma / Q000209:etiology* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor